Issued by
National Human Genome Research Institute (NHGRI)
Office of Behavioral and Social Sciences Research (OBSSR)

Purpose

The National Human Genome Research Institute (NHGRI) along with the Office of Behavioral and Social Sciences Research (OBSSR) announces an administrative supplement program to promote the inclusion of standard phenotypic and environmental exposure measures selected from the PhenX Toolkit (www.phenxtoolkit.org) into existing population-based genomic studies supported by the NIH. The goals of this supplement program are to evaluate the usefulness of PhenX measures and to stimulate their uptake into population studies to enhance genomic research. The inclusion of measures from the PhenX Toolkit will enable researchers to broaden the scope of their studies, examine additional genetic and environmental factors contributing to human health and disease, and combine their studies with other investigators using the same measures to increase power and efficiency of genomic discovery.

Background

NOT-HG-11-001 originally stipulated that applications had to demonstrate availability of large-scale genotyping data at the time of award. This revised Notice seeks to include new and existing large-scale epidemiologic studies, regardless of availability of genotyping data. The applicant needs to demonstrate that 8-10 PhenX measures can be incorporated into the study design.

Genome-wide association (GWA) studies have identified hundreds of associations between genetic variants and complex human diseases, and for some diseases, such as diabetes and Crohn’s disease, pooling of multiple GWA studies by meta-analysis has led to the discovery of new gene associations. However, most GWA studies have had relatively few phenotypic and exposure measures in common. Harmonizing data across studies that have used disparate measures to collect similar information is difficult and time consuming. Development and adoption of standard phenotypic and exposure measures could facilitate the creation of larger, more comprehensive datasets with a variety of phenotype and exposure data for cross-study analysis, thus increasing statistical power and the ability to detect associations of modest effect sizes and gene-gene and gene-environment interactions.

Recognizing the need for standard phenotypic and exposure measures, particularly as related to GWA studies, NHGRI initiated the PhenX Toolkit in 2006 through RFA-HG-00-006, “High-Priority Phenotype and Exposure Measures for Cross-Study Analysis in Genome-Wide Association Studies.” The goal of this three-year program was to identify and catalogue 15 high-quality, well-established, and broadly applicable measures for each of 21 research domains for use in GWA studies and other large-scale genomic research. A PhenX domain is a topic area with a unifying theme such as Demographics, Anthropometrics, Neurology, Cancer, or Social Environments. PhenX measures are selected by Working Groups of domain experts using a consensus process and are made available to the scientific community via the PhenX Toolkit (www.phenxtoolkit.org).

PhenX has met its three-year goal of producing 15 measures in each of 21 domains, but many of the domains were released relatively recently and experience has not been sufficient to gauge the impact of the Toolkit nor potential needs for its continuation. NHGRI has been urged to catalyze adoption of PhenX measures in ongoing genomic studies to obtain timely and needed feedback on the value of the resource including gaps in measures, ease of use, and overall usefulness of the PhenX Toolkit for the research community.

This Notice announces the availability of administrative supplements to NIH-funded projects to support the incorporation of a minimum of 8-10 PhenX measures into genomic research studies that aim to identify the genetic and environmental factors that contribute to health and the development of complex disease. Principal Investigators (PIs) are strongly encouraged to select PhenX measures that are broadly related to a variety of complex traits (e.g., substance use, physical activity, social environment, height, weight, etc.) and not just measures related to the primary phenotypes being evaluated in the parent study. The availability of large-scale genotyping data and adequate consent from participants for deposition of phenotype and/or genotype data into dbGaP are desirable but not required.

PIs should budget for themselves and a data analyst to travel to the Washington, DC area shortly after award for a grantee meeting where they will work together with NHGRI and the PhenX Toolkit grantee, RTI International, to decide upon metrics that will allow a thorough evaluation of the functionality and utility of the PhenX Toolkit, agree upon common approaches for describing and analyzing data collected using the PhenX measures, and identify potential cross-study analyses that can be conducted by all PIs funded under NOT-HG-11-009 or a subgroup of funded PIs. RTI will serve as a facilitator, and if desired, a collaborator in effective incorporation and use of PhenX measures. At a second grantee meeting near the end of the supplement period, PIs will be expected to report findings from analyses of both individual projects and cross-study collaborations when applicable and to provide feedback to NHGRI based on the agreed-upon metrics.

Budget and Funding Information

A total of $700K is anticipated to be provided in Fiscal Year 2011 to support 4-8 supplements for a project duration of one year.

Applicants should use PHS 398 form, see below.

If a no cost extension is necessary, it must be in place per the applicable automatic or prior approval procedures before a supplement request can be awarded.

Administrative supplements are limited to $100,000 direct costs.

Eligibility

This announcement is for supplements to NIH grants meeting the selection criteria outlined in the section titled "Selection."

To be eligible, the PI must be able to demonstrate that the PhenX measures can be administered to sufficient numbers of participants to address the goals of the supplement within the first four months of the award, to ensure that data collection and analysis will be completed by the end of the supplement period. Studies should include sufficient numbers of participants to address the goals of the proposed supplement, and should demonstrate that those numbers will be adequate. Priority will be given to studies with higher numbers of participants; studies with previously generated genotype data; and studies whose participants have been adequately consented for sharing of genomic and/or phenotypic data with the broader research community for a variety of research purposes.

To be eligible, the parent grant must be active and the research proposed in the supplement must be accomplished within the competitive segment. The proposed supplement must be within the general scope of the peer-reviewed activities and aims approved within the parent grant.

IMPORTANT: The research proposed by the NIH grantee in the supplement application must be within the original scope of the NIH-supported grant project. The funding mechanism being used to support this program, administrative supplements, can be used to cover cost increases that are associated with achieving certain new research objectives as long as they are within the original scope of the project. Any cost increases need to result from making modifications to the project in order to take advantage of opportunities that would increase the value of the project consistent with its originally approved objectives and purposes.

Submitting an Administrative Supplement Request

To be considered for an administrative supplement, the request must be signed by the Authorized Organizational Representative/Signing Official (AOR/SO), and must describe the need for additional funding and the categorical costs.

Note: Scope of the overall project and the anticipated contribution of the requested supplement should not exceed five pages.

Submit (1) one original, hard copy of the request packet (with original signatures of the authorized business official) and (2) an electronic copy of the submitted supplement request as a single email attachment in PDF format to the contact listed below:

Requests should be submitted on the PHS398 Application Guide forms (font size and other formatting rules apply as designated in the instructions), as indicated below. Include only the following elements:

Cover Letter which cites this Notice, and the following information:

Project Director/Principal Investigator (PD/PI) name

Parent grant number and title

Amount of the requested supplement

Name and title of the institutional official, and

Phone, email, and address information for both the PD/PI and institutional official.

The cover letter must be signed by the authorized organizational representative/institutional official.

PHS 398 Form Page 1 (Face page)

The title of the project should be the title of the parent award.

This Notice should be cited in Box 2, and the “yes” box should be checked.

The Principal Investigator (PI) must be the same as the PI on the parent award. For Multiple PI parent awards, the Contact PI must be the PI listed on the supplement request, and the supplement cannot change the Multiple PI team.

The remaining items on the face page should be filled out in accordance with the PHS 398 application instructions.

PHS 398 Form Page 2

Note: The project “summary” is that of the administrative supplement, not the parent grant.

A brief proposal describing the project, including:

Scope of the overall project and the anticipated contribution of the requested supplement (not to exceed five pages).

Provide a brief description of the scope of the overall project on which the supplemental request is based.

This section should include a description of the supplement's specific aims, including research design and methods and data analysis. Describe the relationship of the supplement request to the parent grant. Budget for the supplement with a justification that details the items requested, including Facilities and Administrative costs.

Biographical Sketch for all new key personnel (those who are additions on the supplemental project

Human Subjects documentation (if applicable).

Include a current Human Subjects/IRB approval letter, if available. Otherwise, this will be required at the time of funding. All appropriate IRB approvals must be in place prior to a supplement award being made.

Any differences in the involvement or use of human subjects or specimens between the administrative supplement activity and the parent grant should be noted.

When appropriate, details should be provided on the protection of human subjects and inclusion of women, children, and minorities. Additional guidance on Human Subjects Research is provided under Part II of the PHS 398 instructions.

PHS 398 Checklist Form

Selection

Administrative supplement requests will be reviewed administratively by NIH Staff. Selection factors will include the following:

Relevance of the proposed activities to the parent grant

Adequate progress of the parent grant appropriate to the current stage of the project

Appropriate and well-described plan to accomplish the goals within the proposed timeframe that includes a plan demonstrating that the PhenX measures can be administered to a sufficient number of study participants to meet the goals of the supplement within the first four months of award and to ensure that data collection and analysis can be completed within one year

Appropriateness of the selected measures for the study population

Population diversity, particularly in regard to children and minority populations with important health disparities

Public health importance of the traits being studied
Availability of sufficient numbers of participants to meet the goals of the supplement although higher numbers of participants and studies with high quality genotyping on a large number of variants will be given priority

Priority will be given to supplements providing institutional certification to share individual phenotype and/or genotype data through dbGaP

Expertise of the research team proposed to conduct and achieve the goals the supplemental study.

Inquiries

Inquiries and discussion of plans for responding to this Notice are strongly encouraged.